Pergolide is an ergoline derivative which exhibits potent dopaminergic agonist activity and also decreases plasma prolactin concentrations. The compound is therefore useful in treating physiological manifestations associated with hyperprolactinemia. Chemically, pergolide is D-6-n-propyl-8.beta.-methylmercaptomethylergoline. Pergolide mesylate is sold commercially as PERMAX.RTM. for adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease.
Pergolide is known to decompose upon exposure to light (apparently to a sulfoxide species) thus making it necessary to handle the compound and store the ultimate dosage form in light-controlled environments so as to avoid a demonstrable drop in potency of the therapeutic agent. In order to retard this drop in potency, certain stabilizing agents have been incorporated into pharmaceutical compositions containing pergolide which surprisingly reduce the decomposition of this compound when exposed to light; see U.S. Pat. No. 4,797,405.
We have now discovered that pergolide is converted into its sulfoxide during handling in the manufacturing process. This is especially true for preparing tablets with a large excipient to drug ratio --e.g., those containing approximately 50 mcg of pergolide in a tablet of about 300 mg total weight. Under normal manufacturing process, sulfoxide levels of 6-9 percent have been seen immediately after compression of the tablet. Even with special handling, sulfoxide levels are typically 3 percent immediately after the manufacturing process.
We have now discovered that the addition of methionine, cysteine, or cysteine hydrochloride as part of the pharmaceutical composition of pergolide tablets will greatly reduce the formation of the sulfoxide during the manufacturing process.